The role of histamines agonists and antagonists in cervical cancer

Cancer is a debilitating disease which begins with the uncontrolled division of cells from a deregulatory mutation rendering essential stabilatory gene impaired, to being unable to maintain homeostasis and appropriate cellular crosstalk. This progression of cancer has been studied extensively with the most recent research exploring the diversity of cells within a tumour, dubbed the ‘Tumour Microenvironment’ and outlining the hallmarks of cancer, a basis for the tumour to be malignant. Considering the complexity of cancer and the antiquity of its occurrence throughout present times, many different therapies have tried to tackle it at different angles and mechanisms, such as radiotherapy and chemotherapy, causing unwanted side effects due to the lack of specificity for the cancer cells, hence the need for new types of treatment. Drug repurposing is the process of investigating pre-establish drugs that are primarily used for alternative therapy of another malady and using it against cancer ideally without the detrimental side effects and greater efficacy. This project focuses on histamine 2 receptor antagonists and their efficacy against cancer progression primarily used for gastric ulcers and heartburn, and the exploration for the effects of histamine which is expressed locally in the micro vessels of solid tumours. Results show that the targeting of the histamine 2 receptor reduces minimally cell viability of HeLa cervical cancer cells, potentially mitochondrial bioenergetics, whilst treatment with antihistamines showed significant differences in the migration and phenotype of cells. Quantitative gene analysis results showed that the hippo pathway related transcriptional target CTGF was significantly downregulated in most treatments and the cAMP related protein EPAC mostly upregulated, with the cell cycle regulator cyclin D1 and tumorigenic master regulator protein c-MYC being downregulated predominantly . Western blotting and confocal microscopy show a level of nuclear translocation of the Yes-associated protein and a downregulation of the inactive form of phosphorylation Yes-associated protein, part of the oncogenic Hippo-YAP pathway.